PROJECT SUMMARY/ABSTRACT Pulmonary Hypertension (PH) is a progressive and fatal disease of the pulmonary vasculature and right ventricle. In the Pulmonary Vascular Disease Phenomics [PVDOMICS] study, the NHLBI plans to assemble a comprehensive cohort of PH patients across the World Health Organization (WHO) groups 1 through 5, in order to apply phenomic methods and system biology approaches to redefine classifications based on pathobiologic mechanisms. As the Data Coordinating Center (DCC) we will provide the necessary experience in coordination of this complex observational study, the leadership in pulmonary vascular research, and the knowledge in cutting-edge Omics technologies and bioinformatics, which are all essential to achieve the conceptual objective to transform from an arbitrary definition to a biological/treatment-defining classification of PH. The Cleveland Clinic DCC will provide infrastructure, management, participation, oversight, scientific support, and PH expertise for PVDOMICS through four aims. In Aim 1, we set forth the DCC plan the scientific, informatic, administrative support and study operation to carry out PVDOMICS goals to advance the understanding of genetic, pathobiologic, hemodynamic and clinical commonalities and differences among the clinical classifications of PH through phenotypying. In Aim 2, we leverage our expertise in bioinformatics for the development of PVDOMICS controlled vocabularies and metadata elements that can provide the basis for phenomic-based ontology development, and for the design and implementation of a strategy for data collection and analyses that can identify phenotypes based on outcome measures. In Aim 3, we will establish and operate a Biospecimen Lab Core for standardized and secure processing of clinical center samples that are extensively annotated for patient history, medications, diagnostic criteria, risk factors and physiological characteristics, in order to facilitate the Omic studies. Closely linked to the Biospecimen Lab, is a Biospecimen Repository Core, where biosamples will be stored until the end of PVDOMICS, at which time they will be transferred to the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). In Aim 4, we establish and operate central Omics Cores (Genomic, Proteomic, Metabolomic, Coagulomic and Cell Biomic) for effective and reproducible endophenotyping; and Clinical Cores (Imaging, Lung Physiology and Clinical Chemistry) to set standards, quality control and central review of tests and measurements obtained from Clinical Centers for uniform phenotyping. Overall, we plan a DCC infrastructure that will advance PVDOMICS discoveries, facilitate creation of a new pathobiological classification of PH, and set the stage for a future phenomic-based treatment approach for patients with PH.